Complex, High RiskIndicated Interventional

ProceduresHemodynamic Support

Usman Baber, MD MSAssistant Professor of Medicine (Cardiovascular Disease)

Icahn School of Medicine at Mount Sinai New York, NY

Conflict of Interest Disclosure

• Boston Scientific/Astra Zeneca¡ Speaking fees

Defining the CHIP Population

Patient Comorbidities

Ventricular Function/

Hemodynamics

Anatomic Considerations

Are these patients being undertreated?

In order for revascularization to provide a benefit to patients…

• The revascularization being performed has to be performed on disease that is ¡ actually prognostically important or ¡ causing a reduction in quality of life

• The revascularization must be able to be done safely and with high quality and/or durability

Two Goals of Therapy inPatients with SIHD

1. Improve Symptoms and/or Quality of Life– TRY MEDICAL Rx first

Anti-Anginal Agents:An Alternate Perspective

Non-AdherencePolypharmacySide-Effects

Cost

Agent Issues for Patients

“Hard Outcomes” in SIHD

Beta-blockers Sluggishness, fatigue

No benefit unless post-MI or low EF

Nitrates Really need to push for effect No benefit

Ca++ Channel Blockers

Reasonably tolerated No benefit

Ranolazine Cost No benefit

A point rarely discussed: For most patients, GDMT with the ability to affect “hard endpoints” is limited to only aspirin, statins, ACE-I and lifestyle

Two Goals of Therapy inPatients with SIHD

1. Improve Symptoms and/or Quality of Life

2. Improve Prognosis

ACC/AHA SIHD Guidelines:CAD Prognostic Index

*Assuming medical treatment only.

Risk Assessment Algorithm for SIHD Patients

CONFIRM: Association of

Revascularization with All-Cause Mortality

15,223 stable patients without known CAD undergoing CTA

Revascularization of “High-Risk” Anatomy (7.3%) was independently

associated with 62% lower Mortality at 2.1 yrs (adjusted HR 0.38 [0.18,0.83])

Number of Vessels with Severe (>70%) Stenosis

P=0.45 P=0.02 P=0.07

Min JK et al, Eur Heart J 2012

All-

Cau

se M

orta

lity

at

Med

ian

2.1

year

s

LVEF Improvement Post PCI in High-Risk Patients

p=0.02

Pre-PCI Follow-up

31�7

41�1332%

2 Italian Ctrs Study (n=10)Burzotta et al J Card Med 2008

p=0.003

26�634�11

31%

PROTECT I (n=16)Dixon et al. JACC Interv 2009

Pre-PCI Follow-up

p<0.0001

31�1536�14

USpella Registry (n=89)Maini et al. CCI 2012

16%

Pre-PCI Follow-up

p<0.001

27�933�11

PROTECT II (n=175)O�Neill et al. Circ 2012

22%

Pre-PCI Follow-up

Complex, High Risk (Symptomatic) Patients Align with Appropriate Use

• A shift is is afoot in patients presenting to the cath lab

• More risk on stress testing, medications, more symptoms, more anatomy = more likely “appropriate”

Coronary Revascularization Appropriateness Guidelines

Patient Trends

Patel, et al, JACC 2012*

Sym

ptom

s

Complexity

STICH: Mortality in Per-Protocol and Crossover Groups

Doenst et al. Circ Heart Fail. 2013;6:443-450

Mor

talit

y R

ate

1.000.900.800.70

0.40

0.00

Years Following Randomization

Treatments

0 0.5 5.0

MED/MEDCABG/CABG

CABG/MEDMED/CABG

Assigned/Received Assigned/Received

Patients at risk:CABG/CABGCABG/MEDMED/MEDMED/CABG

5555553765

4.54.03.53.02.52.01.51.0

0.10

4874547161

4523443057

4283138154

3192127636

1677

13915

0.300.20

0.500.60

CABG/CABGCABG/MEDMED/CABG

MED/MEDCABG/CABG

MED/MED

:::

HR0.762.010.50

95% CI0.62, 0.921.36, 2.960.30, 0.85

P value0.005

<0.0010.008

How to Improve Complex PCI OutcomesPatient Selection and

Optimization Technical Considerations

Objective assessment of rationale for revascularization

Functionally complete revascularization

Hemodynamic assessment (including valvular disease)

Hemodynamic management(e.g. support)

DAPT candidacy Best-in-class DES,appropriate pharmacology

Comorbidity assessment and management (e.g. Renal fxn)

Lesion preparation / Stent optimization (+/- imaging)

Truly informed consent High-risk lesion expertise(e.g. CTO/LMCA)

Hollenberg Ann Int Med 1999; 131:47-99

Hemodynamic Compromise Pathophysiology

• When a critical mass of LV is necrotic and fails to pump, stoke volume and CO falls

• Myocardial and coronary perfusion are compromised causing tachycardia and hypotension

• Increased LVEDP further decreases coronary perfusion

• Increase LV wall stress increases myocardial oxygen demand

• Lactic acidosis worsens myocardial performance

Patients That Benefit from SupportProtected PCI Cardiogenic Shock Therapy

Why are hemodynamics so essential?

• Catheters can obstruct native aorto-ostial flow (especially

larger catheters). Wires, balloons, stents, devices can obstruct

flow and when inflated by definition are producing ischemia

• Contrast does not contain hemoglobin and is a myocardial

depressant

• Patients may have acute or longstanding LV dysfuction and

CHF

• Adverse hemodynamics will make it difficult to complete the

case and can worsen short/long term outcomes by allowing

…disasters!

Revascularization Strategy by Risk Category

1. Levine GN, et al. J Am Coll Cardiol, 2011 Dec 6;58(24):e44-122, 2 Amsterdam EA, et al. Circulation. 2014 Dec 23; 130(25):e344-426

Low Medium High

Low PCI PCI PCI

Medium CABG or PCI

PCI or CABG Support & PCI

High CABG CABG or PCI Support & PCI

Surgical Risk

Ana

tom

ic R

isk

Protected PCIFDA Indicated

Safe & Effective

ACC/AHA PCI Guidelines1,2

SYNTAXStudy

Often inoperable

Finke et al JACC 2004; 44:340

Cardiac Power Is The Most Important Mortality Predictor in the SHOCK Trial

(Mean Arterial Pressure x Cardiac Output)

451

Cardiac Power =

0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0

0

10

20

30

40

50

60

70

80

90

100

Estim

ated

In-h

ospi

tal M

orta

lity

(%)

Cardiac Power Output

• Multicenter, open-label, randomized study• 600 patients with AMI and cardiogenic shock randomized• Patients allocation in a 1:1 fashion to IAPB support vs. no

support¡ 87% received IABP after PCI

• Efficacy endpoint: 30 days all-cause mortality• Safety endpoint: severe or life-threatening bleeding

according to GUSTO

Thiele et al. NEJM 2010

IABP Shock II: In-hospital and 30 days Results

Thiele et al. NEJM 2010

IABP Shock II: 1-year Results

Thiele et al. Lancet 2013

Impella LV assist device

O2 Demand Cardiac Power OutputO2 Supply

Coronary Flow

MechanicalWork

WallTension

MicrovascularResistance

EDV, EDP AOP Flow

Inflow(ventricle)

Outflow(aortic root)

aorticvalve

Myocardial Protection Systemic Hemodynamic Support

PROTECT-II Trial Design

IMPELLA 2.5 +PCI

IABP + PCI

Primary Endpoint = 30-day Composite MAE* rate

1:1R

Patients Requiring Prophylactic Hemodynamic Support During Non-Emergent High Risk PCI on

Unprotected LM/Last Patent Conduit and LVEF≤35% OR3 Vessel Disease and LVEF≤30%

Follow-up of the Composite MAE* rate at 90 days*Major Adverse Events (MAE) : Death, Stroke/TIA, MI (>3xULN CK-MB or Troponin) , Repeat Revasc, Cardiac or Vascular Operation of Vasc. Operation for limb ischemia, Acute Renal Dysfunction, Increase in Aortic insufficiency, Severe Hypotension, CPR/VT, Angio Failure

Hemodynamic Support Effectiveness:

PROTECT II

CPO= Cardiac Power Output = Cardiac Output x Mean Arterial Pressure x 0.0022

(Fincke R, Hochman J et al JACC 2004; 44:340-348)

Cardiac Power Output

Maximal Decrease in CPO on device

Support from Baseline (in x0.01 Watts)

IABP Impella

N=138 N=141

- 4.2 � 24

- 14.2 � 27

p=0.001

Impella Reduces Peri & Post Procedural MACCE

Dangas et al, Am J Cardiol 2014; 113(2):222-8

MACCE = Death, Stroke, MI, Repeat revasc.

Impella

Time Post Procedure (day)

MA

CC

E (%

)

100 20 30 40 50 60 70 80 90

10

15

20

25

30

p=0.042

IABP

29% reduction

In MACCE

N=216

N=211

MACCE

FDA Approved Randomized

Controlled TrialProtect II

PROTECT II Multivariate analysispredictors of MACCE at 90 days

Odds Ratio Estimate 95% confidence interval P-Value

Per-Protocol Population

Use of atherectomy rotablation during index procedure

1.2984 0.9374 – 1.7983 0.1161

Renal Insufficiency 1.2324 0.9545 – 1.5912 0.1089

Baseline worst TIMI flow: 0-1 1.3112 0.9596 - 1.7918 0.00889

Device: IMPELLA vs IABP 0.7651 0.6099 - 0.9298 0.0206

Intention-To-treat Population

Use of atherectomy rotablation during index procedure

1.2787 0.9251 - 1.7676 0.1366

Renal Insufficiency 1.2466 0.9717 - 1.5992 0.0829

Baseline worst TIMI flow: 0-1 1.2340 0.9089 - 1.6752 0.1777

Device: IMPELLA vs IABP 0.7944 0.6365 - 0.9914 0.0417

Dangas et al, Am J Cardiol 2014; 113(2):222-8

Pump outflow in PA

Pump Outflow

in IVC

Impella RP: Percutaneous Right Ventricular Assist Device (RVAD)

• Transfemoral venous insertion

• 3D shaped cannula

• 22 Fr motor housing

• Pump mounted on a 11Fr catheter

• Flow: 4 L/min @ 33,000 rpm

• Anticoagulation: ACT ~ 160-180 sec

• Approved indication: Extracorporeal circulatory support for up to 6 hrs.

• Medtronic Bio-Medicus arterial cannula, percutaneous access (15-17F)

• Flow 3.5-5 l/minCannula Controller Pump

Tandem Heart : System Components

TandemHeart Randomized trials

• Single center, prospective randomized study between August 2000 and December 2003

• 41 patients with cardiogenic shock complicating AMI enrolled and randomized:

¡ 20 to intra-aortic balloon pump

¡ 21 to TandemHeart

• Primary endpoint:

¡ Haemodynamic improvement • (CPI within 2h post implantation)

• Secondary endpoints:

¡ Heamodynamic and metabolic

parameters

¡ Mortality at 30 days

¡ Device related complications

Thiele et al. EHJ 2004

Thiele et al. EHJ 2004

Complications

• Bleeding

• Limb Ischemia

• DIC

• SIRS

ECMO Percutaneous heart-lung machine

• Centrifugal pump• Hemodynamic support >4.5 l/min• Can increase preload and afterload• No randomized control trials or large

cohorts yet

For VA-ECMO, due to arterial cannula size (in iliacs!), may need to include distal perfusion cannula based upon limb exam, and typically needs surgical explant

ECMO data• Retrospective analysis of 334 patients that underwent PCI due to

AMI and complicated by cardiogenic shock

• Patients undergone procedure in two different periods:¡ 1993-2002à115 patients¡ 2002-2009à219 patients

• ECMO was available in patients in group 2

• Endpoints:¡ TIMI flow¡ 30 days mortality

• Shock versus “profound” shock

Sheu et al. Crit Care Med 2010

Results

Sheu et al. Crit Care Med 2010

P=0.003

Open Questions in Hemodynamic Support

• How much support is necessary?

• What is the role of IABP / Do we believe IABP SHOCK II?

• Which patients should get upfront treatment with an LVAD?

• What is the optimal use for Impella LVAD support?

• Relevance of cost/complications vs. benefit of active LVADs

• How do we manage biventricular failure?

• Is there even a good definition for Shock?

NCDR CathPCI•Cardiogenic shock is defined as a sustained (>30 min) episode of systolic blood pressure <90 mm Hg and/or cardiac index <2.2 L/min per square meter determined to be secondary to cardiac dysfunction and/or the requirement for parenteral inotropic or vasopressor agents or mechanical support (eg, IABP, extracorporeal circulation, VADs) to maintain blood pressure and cardiac index above those specified levels.

NEW YORK STATE•Cardiogenic Shock is defined as an episode of systolic blood pressure <90 mmHg and/or Cardiac Index <2.2 L/min/m2 determined to be secondary to cardiac dysfunction and the requirement for parenteral inotropic or vasopressor agents or mechanical support (e.g., IABP, extracorporeal circulation, VADs) to maintain blood pressure and cardiac index above those specified levels.

Lack of Standard Definitions

Conclusions• There is a large underserved patient population

that can benefit from revascularization!¡ Rather than focusing on low-risk patients who

may be “easy to treat”, we need to focus upon higher-risk patients who have the most to gain

¡ These patients will be more commonly seen¡ The development of comprehensive specialists

trained with advanced technical and cognitive skills to perform these complex, high risk procedures with high quality is sorely needed